Statistical Bioinformatics Seminar: Cuomo

Title: Characterising the effects of genetic variation on gene expression at single-cell
resolution 

Speaker: Dr Anna Cuomo (Garvan Institute) 

Abstract: Single-cell RNA sequencing (scRNA-seq) is widely applied to assess cellular
heterogeneity in human tissues and cell-based models.  Technological advances and
exponential reduction in cost have enabled the first population-scale scRNA-seq studies,
which have assayed single-cell transcriptomes in hundreds of genetically diverse
individuals.  However, current workflows to analyse these data remain primarily based on
principles for analysing conventional bulk expression quantitative trait locus (eQTL)
studies, and hence fail to fully exploit complex scRNA-seq readouts.  A critical
limitation of existing approaches is the need to define discrete cell types for eQTL
mapping a priori, which limits novel opportunities to chart continuous and unbiased
landscapes of regulatory variants.  To address this, we recently proposed CellRegMap, a
statistical framework to map regulatory variants across the continuous manifold of
cellular environments estimated from scRNA-seq.  CellRegMap allows for testing and
characterisation of genetic effects on gene expression at the resolution of individual
cells while flexibly sharing statistical strength related to cell states.  Our framework
provides a principled strategy to identify and characterise heterogeneous genetic
effects that vary across cell states and cell types.  Here, I will describe applications
of CellRegMap on both real and simulated datasets, and describe future challenges in the
broader field of single-cell population genetics.  

About the speaker: Anna completed undergraduate studies (BSc) in Applied Maths at Milano
Polytechnic (Italy), and a MSc in bioinformatics from Delft University of Technology
(Netherlands).  She obtained her PhD at the University of Cambridge and the EMBL-EBI
(UK) co-supervised by Dr.  Oliver Stegle and Dr.  John Marioni.  After a brief bridging
postdoc at the Sanger Institute with Prof.  Nicole Soranzo, she started her current role
as an EMBO Postdoctoral fellow at the Garvan Institute in Sydney (Australia), in the
Joseph Powell and Daniel MacArthur Lab.  Her main interest and expertise lies at the
intersection between single-cell genomics and human genetics, and the development of
statistical models to link DNA variants to single-cell expression profiles.